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Background Pseudomonas aeruginosa (Pa) continues to affect disease progression in cystic fibrosis (CF). However, the best eradication regimen remains unclear. This work compares three different antibiotic eradication regimens in pediatric CF: an administration according to a standard-operating procedure (SOP) order vs. administration outside of this order (ooSOP). Methods This observational study includes all CF patients Results Performed according to SOP order, Hi-TOBI showed the greatest efficacy, followed by lo-Tobra/IV and finally COL/Cip, while ooSOP lo-Tobra/IV was most successful, followed by COL/Cip and Hi-TOBI. Previous Pa-infections and Pa-therapies along with age at CF diagnosis were risk factors for eradication failure. Conclusion Antibiotic treatment in SOP-based pre-defined order leads to significantly better eradication rates than individual modifications of the order of administration. A short course of inhalational high-dose Tobramycin is most successful at the first attempt. Prolonged antibiotic therapy seems to improve eradication after failed initial attempts.

Pulmonary Alveolar Microlithiasis (PAM) is a rare hereditary lung disease caused by biallelic pathogenic variants (pV) in the solute family 34 member 2 gene (SLC34A2; Izumi et al., Am J Respir Crit Care Med 2007; 175: 263–268). pVs in this sodium phosphate co-transporter gene lead to accumulation of calcium phosphate crystals within pulmonary alveoli. More than 1000 cases of PAM were thus far reported, with high variance in disease courses (Stamatis et al., Ann Thorac Surg 1993; 56: 972–975). Frequently, asymptomatic cases are observed, and often times slow disease progression until respiratory insufficiency in middle age occurs (Kosciuk, Eur Respir Rev 2020; 29: 200024). Treatment options for PAM are scarce and largely ineffective, and lung transplantation is the only effective therapy in end-stage disease (Stamatis et al., Ann Thorac Surg 1993; 56: 972–975). Here, we report a novel PAM case in an adolescent migrant from East Africa and discuss current diagnostic and therapeutic options.

Combination therapy with the cystic fibrosis (CF) transmembrane conductance regulator (CFTR) corrector lumacaftor and the CFTR potentiator ivacaftor has demonstrated significant impact on clinical parameters in Phe508del homozygous people with CF. Whether these changes under treatment are correlated to serum levels of both drugs had yet to be investigated. We therefore analyzed data from our previous study (OrkambiFacts, ClinicalTrials.gov Identifier: NCT02807415). In summary, we did not find statistically significant correlations between serum drug levels and changes in clinical parameters and biomarkers of CFTR function such as FEV1, BMI, sweat chloride, nasal potential difference (NPD) and intestinal current measurement (ICM). Absolute blood levels of lumacaftor or ivacaftor do not seem to be informative biomarkers to predict clinical improvement or the attenuation of the basic defect.

Background Serology testing is explored for epidemiological research and to inform individuals after suspected infection. During the coronavirus disease 2019 (COVID-19) pandemic, frontline healthcare professionals (HCP) may be at particular risk for infection. No longitudinal data on functional seroconversion in HCP in regions with low COVID-19 prevalence and low pre-test probability exist. Methods In a large German university hospital, we performed weekly questionnaire assessments and anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immunoglobulin G (IgG) measurements with various commercial tests, a novel surrogate virus neutralisation test, and a neutralisation assay using live SARS-CoV-2. Results From baseline to week 6, 1080 screening measurements for anti-SARS CoV-2 (S1) IgG from 217 frontline HCP (65% female) were performed. Overall, 75.6% of HCP reported at least one symptom of respiratory infection. Self-perceived infection probability declined over time (from mean 20.1% at baseline to 12.4% in week 6, p

Background: Infections, as well as adverse birth outcomes, may be more frequent in migrant women. Schistosomiasis, echinococcosis, and hepatitis E virus (HEV) seropositivity are associated with the adverse pregnancy outcomes of fetal growth restriction and premature delivery. Methods: A cohort study of 82 pregnant women with a history of migration and corresponding delivery of newborns in Germany was conducted. Results: Overall, 9% of sera tested positive for anti-HEV IgG. None of the patients tested positive for anti-HEV IgM, schistosomiasis, or echinococcus serology. Birth weights were below the 10th percentile for gestational age in 8.5% of the neonates. No association between HEV serology and fetal growth restriction (FGR) frequency was found. Conclusions: In comparison to German baseline data, no increased risk for HEV exposure or serological signs of exposure against schistosomiasis or echinococcosis could be observed in pregnant migrants. An influence of the anti-HEV serology status on fetal growth restriction could not be found.

RationaleIn adults, personalised asthma treatment targets patients with type 2 (T2)-high and eosinophilic asthma phenotypes. It is unclear whether such classification is achievable in children.ObjectivesTo define T2-high asthma with easily accessible biomarkers and compare resulting phenotypes across all ages.MethodsIn the multicentre clinical All Age Asthma Cohort (ALLIANCE), 1125 participants (n=776 asthmatics, n=349 controls) were recruited and followed for 2 years (1 year in adults). Extensive clinical characterisation (questionnaires, blood differential count, allergy testing, lung function and sputum induction (in adults)) was performed at baseline and follow-ups. Interleukin (IL)-4, IL-5 and IL-13 were measured after stimulation of whole blood with lipopolysaccharide (LPS) or anti-CD3/CD28.Measurements and main resultsBased on blood eosinophil counts and allergen-specific serum IgE antibodies, patients were categorised into four mutually exclusive phenotypes: “atopy-only”, “eosinophils-only”, “T2-high” (eosinophilia + atopy) and “T2-low” (neither eosinophilia nor atopy). The T2-high phenotype was found across all ages, even in very young children in whom it persisted to a large degree even after 2 years of follow-up. T2-high asthma in adults was associated with childhood onset, suggesting early origins of this asthma phenotype. In both children and adults, the T2-high phenotype was characterised by excessive production of specific IgE to allergens (pConclusionsUsing easily accessible biomarkers, patients with T2-high asthma can be identified across all ages delineating a distinct phenotype. These patients may benefit from therapy with biologicals even at a younger age.

Comprehensive studies investigated the role of T-cells in asthma which led to personalised treatment options targeting severe eosinophilic asthma. However, little is known about the contribution of B-cells to this chronic inflammatory disease. In this study we investigated the contribution of various B-cell populations to specific clinical features in asthma.In the All Age Asthma Cohort (ALLIANCE), a subgroup of 154 adult asthma patients and 28 healthy controls were included for B-cell characterisation by flow cytometry. Questionnaires, lung function measurements, blood differential counts and allergy testing of participants were analysed together with comprehensive data on B-cells using association studies and multivariate linear models.Patients with severe asthma showed decreased immature B-cell populations while memory B-cells were significantly increased compared with both mild-moderate asthma patients and healthy controls. Furthermore, increased frequencies of IgAWith this study we demonstrate for the first time a significant association of increased IgA

Background Currently, health care systems worldwide are challenged with providing care to an increasing number of migrants, refugees, and displaced persons. In this article, we report on disease burden and drug prescription patterns in a large refugee cohort in Germany. Methods We conducted a cross-sectional study of anonymized medical records including demographic data, diagnoses, and drug prescriptions in two refugee reception centres between 2015 and 2019. Refugees and migrants received medical assistance exclusively through the on-site clinics. Thus, this study represents all medical visits of the housed residents. Results In total, n = 15531 diagnoses from n = 4858 patients in a cohort of n = 10431 accommodated refugees were recorded. N = 11898 medications were prescribed. Overall, 29.8% of all refugees sought medical attention. Half of the patients were female (49.6%), the average age was 23.8 years (SD [standard deviation] 17.0, min 0, max 81), and 41.5% were minors (

BackgroundNasal potential difference (NPD) and intestinal current measurements (ICM) are cystic fibrosis transmembrane conductance regulator (CFTR) biomarkers recommended to make a diagnosis in individuals with inconclusive sweat test and CFTR genetics and a clinical suspicion for cystic fibrosis (CF) or CFTR-related disorder (CFTR-RD).MethodsNPD and ICM were measured according to standard operating procedures of the European Cystic Fibrosis Society Diagnostic Network Working Group.ResultsWe assessed 219 individuals by NPD or ICM who had been referred to our laboratory due to clinical symptoms suggestive of CF, but inconclusive sweat test and CFTR genetics (median age: 16.3 years, range 0.4 to 76 years). CF or CFTR-related disorder was diagnosed in 22 of 29 patients (76%) with a CFTR genotype of unknown or variable clinical significance and in 51 of 190 carriers (27%) of one (35/42) or no (16/148) identified CFTR mutation. If two CFTR sequence variants had been identified, the outcome of NPD and ICM was consistent with the classification of the CFTR2 database. Moreover, a suspected false-positive diagnosis of CF was confirmed in seven and withdrawn in eight patients. Of 26 individuals assessed by both NPD and ICM, eleven individuals exhibited discordant tracings of ICM and NPD, with one measurement being in the CF range and the other in the normal range.ConclusionThe majority of patients whom we diagnosed with CF or CFTR-RD by extended electrophysiology are carriers of the wild-type CFTR coding sequence on at least one of their CF alleles. The disease-causing genetic lesions should reside in the non-coding region of CFTR or elsewhere in the genome, affecting the regulation of CFTR expression in a tissue-depending fashion which may explain the large within-group variability of CFTR activity in the respiratory and intestinal epithelium seen in this group.

Background: Migrant women may have an increased risk of adverse birth outcomes. This study analyses the occurrence of low birth weight, preterm birth and intrauterine growth restriction (IUGR) in pregnant migrants. Method: Cross-sectional study of 82 mother-child pairs of pregnant migrants attending medical care in Germany.Results: Median age was 27 years, 49% were of oriental-asian ethnicity and median year of migration was 2015. At least one previous pregnancy was reported in 76%. Delivery mode was caesarian section in 40%. Median gestational age was 39.7 weeks. Preterm birth occurred in 6.1%. Median gestational age for preterm birth was 32.3 weeks. Low birth weight (Conclusions: Compared to German data no increased occurrence of low birth weight, preterm birth or IUGR was found. Of note, rate of caesarian section was higher than in the general population for reasons yet to be identified. The authors propose stratification according to migration status for the national documentation of birth outcomes in Germany.Trial registration: ClinicalTrails.gov, NCT03158298. Registered 18 May 2017 - Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT03158298

BackgroundSerology testing is explored for epidemiological research and to inform individuals after suspected infection. During the COVID-19 pandemic, frontline healthcare professionals (HCP) may be at particular risk for infection. No longitudinal data on functional seroconversion in HCP in regions with low COVID-19 prevalence and low pre-test probability exist.MethodsIn a large German university hospital, we performed weekly questionnaire assessments and anti-SARS-CoV-2 IgG measurements with various commercial tests, a novel surrogate virus neutralization test, and a neutralization assay using live SARS-CoV-2.ResultsFrom baseline to week six, n=1,080 screening measurements for anti-SARS CoV-2 (S1) IgG from n=217 frontline HCP (65% female) were performed. Overall, 75.6% of HCP reported at least one symptom of respiratory infection. Self-perceived infection probability declined over time (from mean 20.1% at baseline to 12·4 % in week six, pConclusionWhen assessing anti-SARS-CoV-2 immune status in individuals with low pre-test probability, we suggest confirming positive results from single measurements by alternative serology tests or functional assays. Our data highlight the need for a methodical serology screening approach in regions with low SARS-CoV-2 infection rates.

Background:The COVID-19 pandemic has disrupted healthcare systems worldwide. Besides the direct impact of the virus on morbidity and mortality of patients, the effect of lockdown strategies on health and healthcare utilization become more and more apparent. Little is known on the effect of the pandemic on pediatric healthcare utilization. We examined the impact of the pandemic on pediatric emergency healthcare.Methods: We conducted a monocentric, retrospective analysis of n=5.424 pediatric emergency visits between January 1st and April 19th of 2019 and 2020, and compared healthcare utilization in the month post lockdown 2020 to the same period in 2019.Results: In the four weeks after lockdown in Germany began, we observed a massive drop of 63.8% in pediatric emergency healthcare utilization (mean daily visits 26.8 ±SEM 1.5 in 2019 vs. 9.7 ±SEM 1 in 2020, pConclusion: Our data illustrate a significant decrease in pediatric emergency room visits during the COVID-19 pandemic. Public outreach is needed to encourage parents to seek medical attention for pediatric emergencies in spite of the pandemic.

Background The COVID-19 pandemic has disrupted healthcare systems worldwide. In addition to the direct impact of the virus on patient morbidity and mortality, the effect of lockdown strategies on health and healthcare utilization have become apparent. Little is known on the effect of the pandemic on pediatric and adolescent medicine. We examined the impact of the pandemic on pediatric emergency healthcare utilization. Methods We conducted a monocentric, retrospective analysis of n = 5,424 pediatric emergency department visits between January 1st and April 19th of 2019 and 2020, and compared healthcare utilization during the pandemic in 2020 to the same period in 2019. Results In the four weeks after lockdown in Germany began, we observed a massive drop of 63.8% in pediatric emergency healthcare utilization (mean daily visits 26.8 ± SEM 1.5 in 2019 vs. 9.7 ± SEM 1 in 2020, p p p Conclusions Our data illustrate a significant decrease in pediatric emergency department visits during the COVID-19 pandemic. Public outreach is needed to encourage parents and guardians to seek medical attention for pediatric emergencies in spite of the pandemic.

Background A recent single-centre study demonstrated that MRI is sensitive to detect early abnormalities in the lung and response to therapy in infants and preschool children with cystic fibrosis (CF) supporting MRI as an outcome measure of early CF lung disease. However, the feasibility of multicentre standardisation remains unknown. Objective To determine the feasibility of multicentre standardisation of chest MRI in infants and preschool children with CF. Methods A standardised chest 1.5 T MRI protocol was implemented across four specialised CF centres. Following training and initiation visits, 42 infants and preschool children (mean age 3.2 ± 1.5 years, range 0–6 years) with clinically stable CF underwent MRI and chest X-ray (CXR). Image quality and lung abnormalities were assessed using a standardised questionnaire and an established CF MRI and CXR score. Results MRI was successfully performed with diagnostic quality in all patients (100%). Incomplete lung coverage was observed in 6% and artefacts also in 6% of sequence acquisitions, but these were compensated by remaining sequences in all patients. The range of the MRI score in CF patients was similar across centres with a mean global MRI score of 13.3 ± 5.8. Cross-validation of the MRI against the CXR score revealed a moderate correlation (r = 0.43–0.50, p Conclusion Our results demonstrate that multicentre standardisation of chest MRI is feasible and support its use as radiation-free outcome measure of lung disease in infants and preschool children with CF.

Purpose Refugees often live in confined housing conditions with shared kitchen and sanitary facilities, rendering susceptible to communicable diseases. We here describe the outbreak, spread and self-limiting nature of a norovirus outbreak in a German refugee camp in the winter of 2015. Methods During a norovirus outbreak, data on clinical symptoms, nationality and living conditions was obtained in a refugee camp in northern Germany in the winter of 2015. Furthermore secondary data on norovirus outbreaks in 2015 was assessed. Results Amongst n = 982 refugees, n = 36 patients (3.7 %) presented with acute norovirus gastroenteritis. The vast majority of cases were children, only the first patient was admitted to the hospital. Intensified hygiene measures were implemented on day 2 of the outbreak, but new cases peaked on day 21 and occurred until one month after the first case. Different cultural backgrounds, eating habits and hygiene standards amongst the refugees made it particularly challenging to implement stringent isolation and hygiene measures. Despite these predisposing factors, only minor norovirus outbreaks were reported in refugee camps in 2015. Conclusion Adults refugees had a low attack rate of symptomatic norovirus infection, while small children are at high risk. Infection spreads despite hygiene measures and camp sites and staff should be prepared for the particular challenges of such situations with a particular focus on cultural-background specific implementation of hygiene measures.

Introduction The current extent of migration to the European continent is associated with exceptional humanitarian challenges. In 2015, Western Europe faced an enormous immigration of refugees with largely unknown protection status against communicable diseases. To adapt vaccination strategies, we aimed at assessing seroprevalences against three of the most relevant vaccine preventable diseases (VPD) in a large representative cohort. Methods IgG seroprevalences for rubella, varicella (n = 554) and measles (n = 552) were analyzed in inhabitants of a Northern German refugee camp in the summer of 2015. Results Of the refugees, 77.9% were male (mean age 27.4 years for male and 26.8 years for female migrants). Most refugees came from the Eastern Mediterranean region (83.4%), followed by immigrants from Eastern Europe (7.4%), Africa (4.6%), or other regions (4.5%). The vast majority of migrants were protected against the three VPD: overall IgG seropositivity was 88.5% for measles, 77.9% for rubella and 95.9% for varicella. However, seroprevalences showed age- and origin-dependent differences. Varicella immunity, for example, was lowest in the youngest age group of both genders (10.1% of male/4.5% of female seronegative refugees 49 years of age), and Sudanese migrants displayed particularly low rates of protection against varicella. Conclusion In accordance with previous studies, our analyses show an overall satisfactory seropositivity against measles, rubella, and varicella in refugees entering Europe during the current exodus. However, this rate is not sufficient for preventing transmission. For example, the rate of 12.9–17.9% female refugees at reproductive age unprotected against measles and the low protection levels against varicella in minors observed in our cohort emphasizes the need for stringent vaccination strategies in refugees coming to Europe during the current crisis.

Background: Currently, half of the population displaced worldwide is children and adolescents. Little is known on healthcare demand in underage migrants. Materials and Methods: We analyzed healthcare utilization in n = 1.411 children and adolescents living in a large German refugee reception in 2015-2016. Results: The mean age of all included refugees was 9 years (60.8% male). The majority came from the eastern Mediterranean region. During a mean camp inhabitance of 34 days, 57.6% needed primary healthcare, with a significant inverse correlation of healthcare seeking frequency with age and duration of camp inhabitance. Infants and unaccompanied minors displayed particular high demands for medical help. Discussion: Our analysis showed that pediatric primary healthcare in pediatric and adolescent refugees are most sought during the first period upon arrival with particular demand in infants, toddlers, and unaccompanied minors. Based on this data, future care taking strategies should be adapted accordingly.

INTRODUCTION Foreign body (FB) aspiration is a frequent and preventable source of morbidity and mortality, especially in children under 4 years of age. Few comprehensive studies exist on presentation and outcome of apple aspirations in children. METHODS In a retrospective analysis of bronchoscopy records of a tertiary medical care center from January 2007 to August 2019, we identified pediatric cases of suspected apple aspirations. RESULTS A total of 11 suspected apple aspirations were identified (observation time 12.7 years, n = 5858 bronchoscopies, n = 226 interventions due to suspected FB aspirations in total). The mean age of patients was 24 months (standard error mean, 7 months; range, 8-83 months), and 6 out of 11 cases (55%) were male. Bronchoscopy confirmed apple aspiration in n = 6/11 cases (55%). In n = 2/11 cases (18%), a bite of the apple was located in the esophagus causing significant tracheal narrowing, and in n = 3/11 cases (27%), no FB was found. In all cases of airway FB identification, extraction was successful. Hypersalivation was associated with esophageal FB location, whereas persistent cough, stridor, or dyspnea were associated with airway FB location. Outcomes ranged from complete reconstitution 1 day after bronchoscopy in most cases to hypoxemia with severe brain damage in one patient. DISCUSSION This analysis shows that apple aspirations are not entirely uncommon in children and may lead to disastrous complications. Typical signs of airway location are persistent cough, stridor or dyspnea, whereas hypersalivation may point toward an esophageal location. In each case of suspected apple aspiration, timely bronchoscopy with possible FB extraction should be performed by an experienced team.

Current political crises in the Middle East and economic discrepancies led millions of people to leave their home countries and to flee to Western Europe. This development raises unexpected challenges for receiving health care systems. Although pan-European initiatives strive for updated and optimized vaccination strategies, little data on immunity against vaccine-preventable diseases in the current refugee population exist. We quantified serum IgG against tetanus and diphtheria (TD) in n = 678 refugees currently seeking shelter in six German refugee centers. Reflecting current migration statistics in Europe, the median age within the cohort was 26 years, with only 23.9 % of female subjects. Insufficient IgG levels without long-term protection against tetanus were found in 56.3 % of all refugees. 76.1 % of refugees had no long-term protection against diphtheria. 47.7 % of subjects needed immediate vaccination against tetanus, and 47.7 % against diphtheria. For both diseases, an age-dependent decline in protective immunity occurred. We observed a considerably low rate of tetanus-protected refugees, and the frequency of diphtheria-immune refugees was far from sufficient to provide herd immunity. These findings strongly support recent intentions to implement and enforce stringent guidelines for refugee vaccination in the current crisis.

Background: Infections are a leading cause of refugee morbidity. Recent data on the rate of airway infections and factors influencing their spread in refugee reception centers is scarce. Methods: A retrospective, cross-sectional study of de-identified medical records with a focus on respiratory infections in underage refugees was conducted at two large German refugee reception centers. Results: In total, medical data from n = 10,431 refugees over an observational period of n = 819 days was analyzed. Among pediatric patients (n = 4289), 55.3% presented at least once to the on-site medical ward with an acute respiratory infection or signs thereof. In 38.4% of pediatric consultations, acute airway infections or signs thereof were present. Airway infections spiked during colder months and were significantly more prevalent amongst preschool and resettled children. Their frequency displayed a positive correlation with the number of refugees housed at the reception centers. Conclusions: We show that respiratory infections are a leading cause for morbidity in young refugees and that their rate is influenced age, season, status, and residential density. This illustrates the need to protect refugee children from contracting airway infections which may also reduce the spread of coronavirus disease 2019 (COVID-19) during the current pandemic.

Rationale: Cystic fibrosis (CF) lung disease starts in early infancy, suggesting that preventive treatment may be most beneficial. Lung clearance index (LCI) and chest magnetic resonance imaging (M...

Background Cystic fibrosis (CF) continues to be the most common life-limiting chronic pulmonary disease in adolescents and young adults. Treatment of CF demands a high treatment time investment to slow the progression of lung function decline, the most important contributor to morbidity and mortality. Adherence is challenging in CF due to the high treatment burden and the lack of immediate health consequences in case of nonadherence. Lung function decline is particularly pronounced in the transition phase between 12 and 24 years of age. The improvement of self-management and self-responsibility and independence from parents and desire for normalcy are conflicting aspects for many adolescents with CF, which influence adherence to the time-consuming pulmonary therapy. Mobile health (mHealth) care apps could help to support self-management and independence and thereby reconcile seemingly conflicting goals to improve adherence, quality of life, and ultimately CF life expectancy. Objective This study aimed to (1) assess user behavior and satisfaction among adolescents and young adults with CF over an observation period of three months using an mHealth app; (2) identify areas of improvement for this mHealth app; and (3) compare overall and disease-specific satisfaction, lung function, and anthropometry before and after using the mHealth app. Methods A total of 27 adolescents and young adults with CF (age range 12-24 years, mean age 16 years, SD 3 years; 14 females, 11 males) used a free mHealth app for three months of whom 25 provided questionnaire data for analysis at the end of the study. Data collection was carried out using questionnaires on usage characteristics and life satisfaction, and standardized assessment of lung function and anthropometry. Results The use of the reminder function for medication declined from 70% (15/21) of the participants at week 4 to 65% (13/20) at week 8 of the observation period. At the end of the study, only 17% (4/23) of the participants wanted to continue using the app. Nevertheless, 56% (14/25) of participants saw the mobile app as a support for everyday life. Potential improvements targeting hedonistic qualities were identified to improve mHealth app adherence. Comparisons of satisfaction with different life aspects hinted at improvements or stabilization for the subitem respiration and the subitem lack of handicap by CF, suggesting that app use might stabilize certain CF-specific aspects of the weighted satisfaction with life. Lung function and anthropometry were not affected consistently. Conclusions Most of the patients did not want to continue using the app after the study period. Only a few CF-specific aspects of weighted life satisfaction were possibly stabilized by the mHealth app; clinical parameters were not affected. Adaptation of the functions to adolescent-specific needs could improve the long-term use and thus positively affect the disease course.

BACKGROUND Cystic fibrosis (CF) continues to be the most common life-limiting chronic pulmonary disease in adolescents and young adults. Treatment of CF demands a high treatment time investment to slow the progression of lung function decline, the most important contributor to morbidity and mortality. Adherence is challenging in CF due to the high treatment burden and the lack of immediate health consequences in case of nonadherence. Lung function decline is particularly pronounced in the transition phase between 12 and 24 years of age. The improvement of self-management and self-responsibility and independence from parents and desire for normalcy are conflicting aspects for many adolescents with CF, which influence adherence to the time-consuming pulmonary therapy. Mobile health (mHealth) care apps could help to support self-management and independence and thereby reconcile seemingly conflicting goals to improve adherence, quality of life, and ultimately CF life expectancy. OBJECTIVE This study aimed to (1) assess user behavior and satisfaction among adolescents and young adults with CF over an observation period of three months using an mHealth app; (2) identify areas of improvement for this mHealth app; and (3) compare overall and disease-specific satisfaction, lung function, and anthropometry before and after using the mHealth app. METHODS A total of 27 adolescents and young adults with CF (age range 12-24 years, mean age 16 years, SD 3 years; 14 females, 11 males) used a free mHealth app for three months of whom 25 provided questionnaire data for analysis at the end of the study. Data collection was carried out using questionnaires on usage characteristics and life satisfaction, and standardized assessment of lung function and anthropometry. RESULTS The use of the reminder function for medication declined from 70% (15/21) of the participants at week 4 to 65% (13/20) at week 8 of the observation period. At the end of the study, only 17% (4/23) of the participants wanted to continue using the app. Nevertheless, 56% (14/25) of participants saw the mobile app as a support for everyday life. Potential improvements targeting hedonistic qualities were identified to improve mHealth app adherence. Comparisons of satisfaction with different life aspects hinted at improvements or stabilization for the subitem respiration and the subitem lack of handicap by CF, suggesting that app use might stabilize certain CF-specific aspects of the weighted satisfaction with life. Lung function and anthropometry were not affected consistently. CONCLUSIONS Most of the patients did not want to continue using the app after the study period. Only a few CF-specific aspects of weighted life satisfaction were possibly stabilized by the mHealth app; clinical parameters were not affected. Adaptation of the functions to adolescent-specific needs could improve the long-term use and thus positively affect the disease course.

The combination of the CFTR corrector lumacaftor with the potentiator ivacaftor has recently been approved for the treatment of patients with cystic fibrosis (CF) homozygous for the Phe508del CFTR mutation. The pivotal phase 3 trials examined clinical outcomes, but did not evaluate CFTR function in patients. Hence, we wanted to examine the effect of lumacaftor-ivacaftor on biomarkers of CFTR function in Phe508del homozygous CF patients aged 12 years and older. This prospective observational study assessed clinical outcomes including FEV1 % predicted and BMI, and CFTR biomarkers including sweat chloride concentration, nasal potential difference (NPD) and intestinal current measurement (ICM) before and 8-16 weeks after initiation of lumacaftor-ivacaftor therapy. A total of 53 patients were enrolled in the study and 52 patients had baseline and follow up measurements. After initiation of lumacaftor-ivacaftor, sweat chloride concentrations were reduced by 18 mmol/L. Further, NPD and ICM showed partial rescue of CFTR function in nasal and rectal epithelia to levels of 10% and 18% of normal, respectively. All patients improved in at least one CFTR biomarker, but no correlations were found between CFTR biomarker responses and clinical outcomes. We could show that lumacaftor-ivacaftor results in partial rescue of Phe508del CFTR function to levels comparable to the lower range of CFTR activity found in patients with residual function mutations. Functional improvement was detected even in the absence of short-term improvement of FEV1 % predicted and BMI.

Background: Immigration into Europe has reached an all-time high. Provision of coordinated healthcare, especially to refugee women that are at increased risk for adverse pregnancy outcomes, is a challenge for receiving health care systems. Methods: We assessed pregnancy rates and associated primary healthcare needs in three refugee cohorts in Northern Germany during the current crisis. Results: Out of n = 2911 refugees, 18.0% were women of reproductive age, and 9.1% of these were pregnant. Pregnancy was associated with a significant, 3.7-fold increase in primary health care utilization. Language barrier and cultural customs impeded healthcare to some refugee pregnant women. The most common complaints were demand for pregnancy checkup without specific symptoms (48.6%), followed by abdominal pain or urinary tract infections (in 11.4% of cases each). In 4.2% of pregnancies, severe complications such as syphilis or suicide attempts occurred. Discussion: We present data on pregnancy rates and pregnancy associated medical need in three current refugee cohorts upon arrival in Germany. Healthcare providers should be particularly aware of the requirements of pregnant migrants and should adapt primary caretaking strategies accordingly.

During the current period of immigration to Western Europe, national healthcare systems are confronted with high numbers of asylum seekers with largely unknown health status. To improve care taking strategies, we assessed healthcare utilization in a large, representative cohort of newly arriving migrants consisting of n = 1533 residents of a reception center in Northern Germany in 2015. Most asylum seekers were young, male adults, and the majority came from the Eastern Mediterranean region. Overall, we observed a frequency of 0.03 visits to the onsite primary healthcare ward per asylum seeker and day of camp residence (IQR 0.0–0.07, median duration of residence 38.0 days, IQR 30.0–54.25). Female asylum seekers showed higher healthcare utilization rates than their male counterparts, and healthcare utilization was particularly low in asylum seekers in their second decade of life. Furthermore, a significant correlation between time after camp entrance and healthcare utilization behavior occurred: During the first week of camp residence, 37.1 visits/100 asylum seekers were observed, opposed to only 9.5 visits/100 asylum seekers during the sixth week of camp residence. This first data on healthcare utilization in a large, representative asylum seeker cohort entering Western Europe during the current crisis shows that primary care is most needed in the first period directly after arrival. Our dataset may help to raise awareness for refugee and migrant healthcare needs and to adapt care taking strategies accordingly.

Background: In 2015, a high number of refugees with largely unknown health statuses immigrated to Western Europe. To improve caretaking strategies, we assessed the prevalence of latent tuberculosis infection (LTBI) in a refugee cohort. Methods: Interferon-Gamma release assays (IGRA, Quantiferon) were performed in n = 232 inhabitants of four German refugee centers in the summer of 2015. Results: Most refugees were young, male adults. Overall, IGRA testing was positive in 17.9% (95% CI = 13.2&ndash, 23.5%) of subjects. Positivity rates increased with age (0% &lt, 18 years versus 46.2% &gt, 50 years). Age was the only factor significantly associated with a positive IGRA in multiple regression analysis including gender, C reactive protein, hemoglobin, leukocyte, and thrombocyte count and lymphocyte, monocyte, neutrophil, basophil, and eosinophil fraction. For one year change in age, the odds are expected to be 1.06 times larger, holding all other variables constant (p = 0.015). Conclusion: Observed LTBI frequencies are lower than previously reported in similar refugee cohorts. However, as elderly people are at higher risk for developing active tuberculosis, the observed high rate of LTBI in senior refugees emphasizes the need for new policies on the detection and treatment regimens in this group.

Currently, vast numbers of migrants with largely unknown health statuses have been entering Europe. To improve care taking strategies, prevalence, severity and types of anemia in a large refugee cohort were assessed. Blood counts were performed in n = 787 inhabitants from six German refugee centers. Most included migrants were young, male adults. Anemia was present in 22.5% of subjects with an age-dependent prevalence increase (7.9% > 18 years vs. 30.8% > 50 years). More females than males were anemic (27.1% vs. 20.4%). The majority of affected migrants had mild anemia (86.2%) of either normocytic/normochromic (55.9%) or microcytic/hypochromic (20.9%) type. Observed anemia frequencies are in accordance with global anemia prevalence recently estimated by the WHO. However, the observed high rates of anemia particularly in female and older refugees emphasize the need for adapted care taking strategies in refugee medicine. Further evaluation of causes of anemia in the migrating population is needed.

The combination of the CFTR (cystic fibrosis transmembrane conductance regulator) corrector lumacaftor with the potentiator ivacaftor has been approved for the treatment of patients with cystic fibrosis homozygous for the Phe508del CFTR mutation. The phase 3 trials examined clinical outcomes but did not evaluate CFTR function in patients.To examine the effect of lumacaftor-ivacaftor on biomarkers of CFTR function in Phe508del homozygous patients with cystic fibrosis aged 12 years and older.This prospective observational study assessed clinical outcomes including FEVA total of 53 patients were enrolled in the study, and 52 patients had baseline and follow-up measurements. After initiation of lumacaftor-ivacaftor sweat chloride concentrations were reduced by 17.8 mmol/L (interquartile range [IQR], -25.9 to -6.1; P 0.001), nasal potential difference showed partial rescue of CFTR function in nasal epithelia to a level of 10.2% (IQR, 0.0-26.1; P 0.011), and intestinal current measurement showed functional improvement in rectal epithelia to a level of 17.7% of normal (IQR, 10.8-29.0; P 0.001). All patients improved in at least one CFTR biomarker, but no correlations were found between CFTR biomarker responses and clinical outcomes.Lumacaftor-ivacaftor results in partial rescue of Phe508del CFTR function to levels comparable to the lower range of CFTR activity found in patients with residual function mutations. Functional improvement was detected even in the absence of short-term improvement of FEV

The current extent of migration poses emerging socio–economic and humanitarian challenges. Little is known on vaccination rates in migrants entering Europe, and the implementation of guidelines for serological testing and vaccination of refugees are pending. We conducted seroprevalence analyses for measles, mumps, rubella and varicella (MMRV) in 678 refugees coming to Germany during the current crisis. The mean age of refugees was 28.8±11.4 years, and 76.1 % of subjects were male. Overall, IgG seronegativity was 7.4 % (95 % CI 5.5-9.6) for measles, 10.2 % (95 % CI 8.0-12.5) for mumps, 2.2 % (95 % CI 1.2-3.4) for rubella, and 3.3 % (95 % CI 1.9-4.9) for varicella. Seropositivity rates were age-dependent with considerably low values in children. For example, overall MMR immunity was 90.9 % (95 % CI 88.8-93.1), but only 73.1 % of minor aged refugees displayed complete seroprevalence against all three diseases, and only 68.9 % of children and adolescents were completely MMRV immune. Our initial data set suggests overall satisfactory MMRV immunity in adult migrants coming to Europe, but the observed low MMRV seroprevalences in refugee children support thorough and prompt vaccination of young migrants entering Europe. Taken together, our data set underlines the urgent need to implement and validate vaccination guidelines for refugee care in the current crisis.

Background Circumstantial evidence suggests that conjugated linoleic acid (CLA) beneficially modulates immune function in allergic subjects. C9,t11-CLA, naturally occurring in ruminant fats, is suggested to be the effective isomer. In contrast, for the t10,c12-CLA isomer, which is naturally found only in traces but usually constitutes a relevant part in commercial CLA mixtures, adverse effects have been reported. Aim of this study was to assess putative immunomodulatory effects of highly enriched c9,t11-CLA in allergic subjects. To our best knowledge, our study is the first in that a CLA preparation was used for such purpose which was free of t10,c12-CLA. Design Twenty-nine asthmatic children and adolescents (age 6–18 y) with diagnosed allergic sensitization against grass pollen, house dust mite, or cat hair/epithelia consumed daily a portion of yoghurt containing either 3 g CLA (75 % c9,t11-CLA, 87 % purity) or placebo (safflower oil) over a period of 12 weeks. At study start and end, lung function parameters, specific IgE, in vitro allergen-induced cytokine production in peripheral blood mononuclear cells (PBMC), plasma ECP, urinary 8-oxodG as marker of oxidation, fatty acid profiles of erythrocytes, and routine haematological parameters were determined. Prior to blood samplings, 3-days dietary records were requested. Throughout the study, the participants documented daily their peak expiratory flow and kept protocol about their allergy symptoms and usage of demand medication. Results In contrast to the CLA group, PBMC-produced IFN-γ and IL-4 increased significantly and by trend, respectively, in the placebo group. Moreover, plasma ECP tended to increase in the placebo group. In the pollen subgroup, FEV1 improved upon both CLA and placebo oil supplementation. In both intervention groups, the n-6/n-3 PUFA ratio in red blood cells decreased, mainly due to an increase in n-3 PUFA. Moreover, 8-oxodG excretion increased in both groups. No changes occurred regarding specific IgE concentrations, allergy symptoms, and volume parameters. Conclusion Our results indicate that CLA modestly dampens the inflammatory response on the cellular level. A clinically relevant amelioration of the symptoms could not be proved in atopic manifest patients. Trial registration NCT01026506.